title: Dietary restriction in the periconceptional period in normal-weight or obese ewes results in increased abundance of angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor (AT1R) in the absence of changes in ACE or AT1R methylation in the adrenal of the offspring.
abstract: Exposure to dietary restriction during the periconceptional period in either normal or obese ewes results in increased adrenal growth and a greater cortisol response to stress in the offspring, but the mechanisms that programme these changes are not fully understood. Activation of the angiotensin type 1 receptor (AT1R) has been demonstrated to stimulate adrenal growth and steroidogenesis. We have used an embryo transfer model in the sheep to investigate the effects of exposure to dietary restriction in normal or obese mothers from before and 1 week after conception on the methylation status, expression, abundance and localisation of key components of the renin-angiotensin system (RAS) in the adrenal of post-natal lambs. Maternal dietary restriction in normal or obese ewes during the periconceptional period resulted in an increase in angiotensin-converting enzyme (ACE) and AT1R abundance in the absence of changes in the methylation status or mRNA expression of ACE and AT1R in the adrenal of the offspring. Exposure to maternal obesity alone also resulted in an increase in adrenal AT1R abundance. There was no effect of maternal dietary restriction or obesity on ACE2 and AT2R or on ERK, calcium/calmodulin-dependent kinase II abundance, and their phosphorylated forms in the lamb adrenal. Thus, weight loss around the time of conception, in both normal-weight and obese ewes, results in changes within the intra-adrenal RAS consistent with increased AT1R activation. These changes within the intra-adrenal RAS system may contribute to the greater adrenal stress response following exposure to signals of adversity in the periconceptional period.
authors.affiliation: School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia 5000, Australia.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.forename: Janna L
authors.initials: JL
authors.lastname: Morrison
authors.forename: Amreet
authors.initials: A
authors.lastname: Gill
authors.forename: Leewen
authors.initials: L
authors.lastname: Rattanatray
authors.forename: Severence M
authors.initials: SM
authors.lastname: MacLaughlin
authors.forename: David
authors.initials: D
authors.lastname: Kleemann
authors.forename: Simon K
authors.initials: SK
authors.lastname: Walker
authors.forename: I Caroline
authors.initials: IC
authors.lastname: McMillen
mesh_terms: D000311:Adrenal Glands / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D000818:Animals; D017849:Animals, Inbred Strains; D004038:Diet, Reducing / Q000009:adverse effects; D004624:Embryo Transfer; D005260:Female; D005306:Fertilization; D008297:Male; D044342:Malnutrition / Q000150:complications / Q000503:physiopathology*; D018811:Maternal Exposure / Q000009:adverse effects; D008745:Methylation; D009765:Obesity / Q000150:complications / Q000178:diet therapy* / Q000503:physiopathology; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology; D039401:Prenatal Nutritional Physiological Phenomena; D011499:Protein Processing, Post-Translational; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System; D034561:Sheep, Domestic; D013021:South Australia; D015431:Weight Loss
chemical_list: D044140:Receptor, Angiotensin, Type 1; D007703:Peptidyl-Dipeptidase A